Stents reduce the rate of restenosis compared with balloon angioplasty. However, a considerable number of patients still develop restenosis and require repeat revascularization within 6 to 12 months. To overcome this problem, drug-eluting stents coated with a polymer were introduced into interventional cardiology to deliver medication directly to the site of vascular injury. However, this type of stents was found to present the following shortcomings that may still lead to restenosis: "They have caused substantial inflammatory response and increased neointima formation after dissipation of the immuno-suppressants and require further refinement for improvements with respect to biocompatibility." The polymeric coatings may come loose during the enormous mechanical stress of stent expansion and cause additional vessel wall injury. " They do not provide a homogeneous distribution of drugs at the appropriate site. " They do not provide adequate resistance to abrasion. We propose to improve stent design by developing a new technique to produce highly ordered nanopores in the stent material (NiTi and stainless steel (SS) 316 L). The nanopores are subsequently investigated as a suitable carrier for selected drugs, including tacrolimus, rapamycin, and paclitaxel, to combat neointima proliferation. In addition, heparin will be covalently bonded to the proposed materials to reduce the occurrence of thrombosis, especially after dissipation of the drugs. The hypothesis is that our suggested stent design will (1) improve biocompatibility; (2) suppress any risk of mechanical failure since our design eliminates the need for a thick polymeric coating; (3) control the drug-elution process by selecting the appropriate nanopore design (nanopore size, encapsulation of warfarin/fluvastatin); and, (4) improving abrasion and fretting resistance. [unreadable] [unreadable] The specific aims of the proposed project are: "Aim 1 will be to develop the process of fabricating nanoporous NiTi and SS alloys." Aim 2 will be to investigate the drug-loading and drug-release process as a function of nanopore design. "Aim 3 will be to assess the biocompatibility (smooth muscle cell and endothelial cell responses) and the mechanical integrity of these materials. " Aim 4 will be an educational component required for R15 AREA grants to train undergraduate and graduate students [unreadable] [unreadable] Ultimately, the proposed work will provide a novel technology to produce nanoporous functional materials that may prove to be useful in many medical devices that include dental implants (the nanopores are filled with a material that enhances tissue growth) and hip and knee implants (the nanopores may be bio-functionalized to significantly lower friction coefficients and, hence, decrease wear), and other devices that require various drug delivery strategies. PUBLIC HEALTH RELEVANCE: The main objective of the proposed research project is to develop bio-friendly and drug- eluting stents to reduce the occurrence of restenosis in interventional cardiology. The new drug-elution design is different from the traditional approach which consists of stainless steel (SS) or NiTi substrates coated with a drug-eluting polymer. The performance of the newly designed stents is expected to provide results that are far superior to those obtained by traditional ones in terms of reducing the occurrence of restenosis by enhancing biocompatibility, control of drug kinetics, mechanical robustness, and resistance to abrasion. Another important objective of this R15 Academic Research Enhancement Award (AREA) is to train graduate students and expose undergraduate students to a multidisciplinary research environment. [unreadable] [unreadable] [unreadable]